Scientists have used low-intensity electromagnetic fields to treat
cancer patients in trials which they say could lead to the
development of a new type of anti-tumour therapy.

Patients hold a spoon-shaped antenna in their mouths to deliver a
very low-intensity electromagnetic field in their bodies. In
trials of patients with advanced liver cancer, the therapy – given
three times a day – resulted in long-term survival for a small
number of those monitored, the team has reported in the British
Journal of Cancer. Their tumours shrank, while healthy cells in
surrounding tissue were unaffected.

However, the scientists – from the US, Brazil, France and
Switzerland – also stressed that the technique was still in its
infancy and would require several years for further trials to take
place. "This is a truly novel technique," said the team's leader,
Professor Boris Pasche of the University of Alabama, Birmingham.
"It is innocuous, can be tolerated for long periods of time, and
could be used in combination with other therapies."

Pasche added that he had obtained permission from the US Food and
Drug Administration to carry out trials on large groups of
patients and was talking to companies in the US, Asia, South
America, Russia and Europe about raising funds for future
research.

In 2009, Pasche and his colleagues published results in the
Journal of Experimental and Clinical Cancer Research which showed
that low-level electromagnetic fields at precise frequencies –
ranging from 0.1Hz to 114kHz – halted cancer cell growth in small
numbers of patients. Different cancers responded to
electromagnetic fields of different frequencies. Cells in
surrounding, healthy tissue were unaffected.

The exact mechanism for this process was not explained in the
paper. However, results of recent experiments by the team – using
cancer cell cultures in the laboratory and published in the
British Journal of Cancer – suggest that low-level electromagnetic
fields interfere with the activity of genes in cancer cells. In
specific cases, this affected the ability of cancer cells to grow
and divide. The spread of tumours halted and in some cases they
began to shrink.

"This is extremely exciting," said Pasche. "We think the technique
could also be used to treat breast tumours and possibly other
forms of cancer."

The use of electromagnetic fields was also welcomed, cautiously,
by Eleanor Barrie of Cancer Research UK: "This research shows how
specific low frequencies of electromagnetic radiation can slow the
growth of cancer cells in the lab. It's still unclear why the
cancer cells respond in this way, and it's not yet clear if this
approach could help patients, but it's an interesting example of
how researchers are working to find new ways to home in on cancer
cells while leaving healthy cells unharmed."

The use of electromagnetic fields to treat tumours may seem
surprising given recent controversy over claims that fields
generated by mobile phones and electricity pylons can trigger
cancers and leukaemia. However, Pasche stressed that the intensity
of the fields used in his team's experiments were between 100 and
1,000 times lower than those from a mobile phone. "In any case,
the evidence produced from major studies of users of these phones
does not suggest there is a clearly identifiable risk posed by
these electromagnetic fields," he said.

EP1974769MX2009010425ELECTRONIC SYSTEM FOR
INFLUENCING CELLULAR FUNCTIONS IN A WARM-BLOODED MAMMALIAN
SUBJECT.

Disclosed is an electronic system activatable by electrical power.
The system is useful for influencing cellular f unctions or
malfunctions in a warm-blooded mammalian subject. The system
comprises one or more controllable low energy H F (High Frequency)
carrier signal generator circuits, one or more data processors or
integrated circuits for receiving control information, one or more
amplitude modulation control generators and one or more amplitude
modulation frequency control generators. The amplitude modulation
frequency control generators are adapted to accurately control the
frequency of the amplitude modulations to within an accuracy of at
least 1000 ppm, most preferably to within about 1 ppm, relative to
one or more determined or predetermined reference amplitude
modulation frequencies.

FIELD OF THE INVENTION

[0001] This invention relates to an electronic system for
influencing cellular functions in a warm-blooded mammalian
subject. More particularly, the invention concerns research
findings related to how earlier electronic systems may be modified
to achieve both improved and additional therapeutic effects.

BACKGROUND OF THE INVENTION

[0002] Reference is made to European
Patent
EP 0 592 851 B1 and corresponding Patents and Patent
Applications and to the various publications referred to therein.
Since the time of the priority Application filed in the USA on 25
September 1992 ( US Serial No 951563 now USP 5,441,528 ), a number of
further publications related to effects of electromagnetic fields
on patients suffering from insomnia and/or anxiety disorders have
taken place:

[0003] The above publications are related to an earlier device,
system and use thereof described in said EP 0 592 851 B1 . The
improved electronic system and control thereof in accordance with
the present invention, however, has been determined to find
therapeutic application not only for influencing cellular
functions (or malfunctions) leading to CNS disorders, but also for
influencing other cellular functions (or malfunctions) including
particularly directly or indirectly influencing cancerous cell
growth or proliferation thereof in warm-blooded mammalian
subjects. The direct or indirect influence on cancerous cell
growth may involve any of prophylactic avoidance of cancerous cell
formation, influencing of cell functions such as influencing
leukocyte cell functions which can lead to inhibition of cancerous
cell growth or proliferation thereof, or killing of cancerous
cells harboured by a warm-blooded mammalian subject.

[0004] Electromagnetic energy generating devices and use of
electromagnetic energies for treating living mammalian subjects
harbouring cancerous cells described in the literature include:
USP 5,908,441 issued June 1, 1999 to Bare; James E. and the
references cited therein and so-called "NovoCure technology"
involving in vivo implantation of electrodes to either side of
tumorous growths.

SUMMARY OF THE INVENTION

[0005] According to invention, an electronic system is provided
which is activatable by electrical power. The system is employed
to influence cellular functions or malfunctions in a warm-blooded
mammalian subject. The system comprises one or more controllable
low energy electromagnetic energy generator circuits for
generating one or more high frequency carrier signals. One or more
microprocessors or integrated circuits comprising or communicating
with the one or more generator circuits are provided which are
also for receiving control information from a source of control
information. The one or more generator circuits include one or
more amplitude modulation control signal generators for
controlling amplitude modulated variations of the one or more high
frequency carrier signals. The one or more generator circuits
furthermore include one or more programmable amplitude modulation
frequency control signal generators for controlling the frequency
at which the amplitude modulations are generated. The one or more
amplitude modulation frequency control generators are, in terms of
the present invention, adapted to accurately control the frequency
of the amplitude modulations to within an accuracy of at least
1000 ppm relative to one or more determined or predetermined
reference amplitude modulation frequencies selected from within a
range of 0.1 Hz to 50 kHz. The system furthermore comprises a
connection or coupling position for connection or coupling to or
being connected or coupled to an electrically conductive
applicator for applying to the warm-blooded mammalian subject the
one or more amplitude-modulated low energy emissions at said
accurately controlled modulation frequencies.

[0006] The term, "accurately controlled" means that the modulated
low energy electromagnetic emissions should be modulated to within
a resolution of at most 1 Hz of an intended higher frequency
(greater than about 1000 Hz) determined or predetermined
modulation frequencies. For example, if one of the one or more
determined or predetermined modulation frequencies to be applied
to the warm-blooded mammalian subject is 2000 Hz, the accurate
control should lead to such modulated low energy emission being
generated at a frequency of between 1999 and 2001 Hz. However, and
in terms of what has been determined from experiences in treating
human subjects harbouring cancerous cells with the aim of
arresting proliferation or killing of such cells, the accurate
control should lead to a resolution of 0.5, preferably 0.1, more
preferably 0.01 and indeed most preferably 0.001 Hz of the
intended determined or predetermined modulation frequency.

[0007] It is furthermore of importance that the stability of the
emissions is maintained during emission, and that such stability
should be of the order of 10<-5> , preferably 10<-6> ,
and more preferably 10<-7> , stability being the relative
deviation of frequency divided by the desired frequency, e.g. 0,01
Hz (deviation) / 1'000 Hz (desired freq.) = 10<-5> .

[0008] As already described in said EP 0 592 851 B1 , the system
includes a microprocessor (which may more recently be replaced by
an integrated circuit) into which control information is loaded
from an application storage device. The microprocessor (or now
alternatively integrated circuit) then controls the function of
the system to produce the desired therapeutic emission. Also
described is the provision in the system of an impedance
transformer connected intermediate the emitter of low energy
electromagnetic emissions and a probe (here more broadly described
as an electrically conductive applicator) for applying the
emissions to the patient. The impedance transformer substantially
matches the impedance of the patient seen from the emitter circuit
with the impedance of the output of the emitter circuit.

BRIEF DESCRIPTION OF THE DRAWINGS

[0009]

FIG. 1 shows an exemplary casing
structure for the electronic circuit shown in Figure 2, an
applicator 13 (exemplified as a probe suitable for being placed
in the mouth of a patient) and an interface 16 (which may be
replaced by a receiver) for receiving information from a source
of information 52 such as may be comprised in an information
storage device, e.g. of the nature described and illustrated in
Figures 12 to 17 of EP 0 592 851 B1 .

FIG. 2 is a block diagram of
exemplary circuitry which may be comprised in the exemplary
casing structure of FIG. 1. This Figure 2 differs essentially
from Figure 2 of EP 0 592 851 B1 by comprising a highly accurate
modulation frequency generator 31 (named a Digital Direct
Synthesizer or DDS), which enables accurate control of
modulatable oscillator represented by dotted line block 106.

[0010] Reference is made to the various Figures of EP 0 592 851 B1
and the detailed description thereof, a number of which are
exemplary of components which may be comprised in the circuit of
Figure 2.

[0012] Figure 4 of EP 0 592 851
B1 is a detailed schematic of a modulation signal buffer and
carrier oscillator circuit which may be employed in the circuit
of the present FIG. 2;

[0013] FIG. 5 of EP 0 592 851 B1
is a detailed schematic example of an amplitude modulation (AM)
and power generator 34 and output filter 39 which could be
comprised in the circuit of the present FIG. 2;

[0014] FIG. 6 of EP 0 592 851 B1
is a detailed schematic example of an impedance transformer 14
which may be comprised in the circuit of the present FIG. 2;

[0015] FIG. 7 of EP 0 592 851 B1
is a detailed schematic example of an emission sensor 53 which
may be comprised in the circuit of the present FIG. 2;

[0016] FIG. 8 of EP 0 592 851 B1
is a detailed schematic example of an output power sensor
circuit 54 which may be employed in the circuit of the present
FIG. 2.

[0017] FIG. 9 of EP 0 592 851 B1
is a detailed schematic example of a display module or
information output 17 which may be included in the circuit of
the present FIG. 2.

[0018] FIG. 10 of EP 0 592 851 B1
is a detailed schematic example of a power supply control
circuit including battery charger 57 which may be comprised in
the circuit of the present FIG. 2.

[0019] FIGS. 11 a-d of EP 0 592
851 B1 are exemplary flow charts of the method of operation of
the system of FIG's 1 and 2.

DETAILED DESCRIPTION

[0020] Referring to FIG. 1, presented is a modulated low energy
electromagnetic emission application system 11, in accordance with
the present invention. As described in prior U.S. Pat. Nos. 4,649,935 and
4,765,322 , such a system has proven to be useful in the
practice of Low Energy Emission Therapy (LEET, a trademark of
Symtonic S.A. or a successor of this Company), which involves
application of emissions of low energy radio frequency (RF)
electromagnetic waves to a warm-blooded mammalian subject. The
application has proven to be an effective mode of treating a
warm-blooded mammalian subject suffering from central nervous
system (CNS) disorders such as, for example, generalized anxiety
disorders, panic disorders, sleep disorders including insomnia,
psychiatric disorders such as depression, obsessive compulsive
disorders, disorders resulting from substance abuse, sociopathy,
post traumatic stress disorders or other disorders of the central
nervous system.

[0021] The system includes an electrically conductive applicator
12,13 for applying one or more electromagnetic emissions to the
warm-blooded mammalian subject. One form of applicator consists of
a probe or mouthpiece 13 which is inserted into the mouth of a
subject undergoing treatment. Probe 13 is connected to an
electromagnetic energy emitter (see also FIG. 2), through coaxial
cable 12 and impedance matching transformer 14.

[0022] It has previously been considered that an efficient
connection of an electrically conductive applicator to a subject
could only be achieved by means of a probe which is adapted to be
applied to any mucosa of the subject, such as by being located
within oral, nasal, optical, urethral, anal, and/or vaginal
cavities or surfaces. It has however now been determined that in
fact satisfactory application of emissions to a patient can be
achieved by simpler physical contact of the electrically
conductive applicator with the skin of the patient. Emissions to
the patient may, for example be achieved by a conductive,
inductive, capacitive or radiated coupling to the patient. An
example of a coupling found to be effective involving indirect
physical contact with the skin of a patient, is an insulated
applicator to be placed over or within an ear of the patient. The
emissions thus passed to the patient may be both by capacitive and
radiated means. An important advantage of a device which does not
need to be placed in the mouth of a patient is that the patient is
able to speak clearly during a time of treatment. The treatment is
accordingly more user-friendly and leads to enhanced patient
compliance.

[0023] Electronic system 11 also includes a connector or coupler
for connection to a programmable device such as a computer or an
interface or receiver 16 which is adapted to receive an
application storage device 52 such as, for example, magnetic
media, semiconductor media, optical media or mechanically encoded
media, or programmed emissions programmed with control information
employed to control the operation of system 11 so that the desired
type of low energy emission therapy is applied to the patient.

[0024] Application storage device 52 can be provided with a
microprocessor which, when applied to interface 16, operates to
control the function of system 11 to apply the desired low energy
emission therapy. Alternatively, application storage device 52 can
be provided with a microprocessor which is used in combination
with microprocessor 21 within system 11. In such case, the
microprocessor within device 52 could assist in the interfacing of
storage device 52 with system 11, or could provide security
checking functions.

[0025] System 11 also includes a display 17 which can display
various indications of the operation of system 11. In addition,
system 11 includes on and off power buttons 18 and 19, optionally
replaced by user interface 21A (refer to Figure 2).

[0026] Referring to FIG. 2, presented is a block diagram of
exemplary electronic circuitry of system 11, in accordance with
the present invention. A data processor, such as for example,
microprocessor or integrated circuit 21, operates as the
controller for electronic system 11, and is connected to control
the various components of the system 11 through address bus 22,
data bus 23 and input/output lines 25. The FIG. 2 is modified as
compared to FIG.2 of EP 0 592 851 B1 by including what is known as
a Digital Direct Synthesizer (DDS) 31 which operates as a highly
accurate and stable modulation frequency generator within the
system 11. An exemplary DDS device is available from Analog
Devices of Norwood, MA 02062-9106, USA, Part No AD9835. The device
is a numerically controlled oscillator and modulation capabilities
are provided for phase modulation and frequency modulation. As
represented by dotted line block 102, entitled "PROCESSOR WITH
DAC", the functionality of the DDS may also be combined with
microprocessor 21 with digital to analogue converter (DAC).

[0027] Microprocessor 21 preferably includes internal storage for
the operation of a coded control program, and temporary data. In
addition, microprocessor 21 includes input/output ports and
internal timers. Microprocessor 21 may be a microcontroller, for
example microcontrollers 8048 or 8051 available from Intel
Corporation.

[0028] The timing for microprocessor 21 is provided by system
clock oscillator 26A which may be run at any clock frequency
suitable for the particular type of microprocessor used. An
exemplary clock frequency is 8.0 MHz. Oscillator 26A may be
replaced by reference frequency oscillator 26 which secures the
stability of the accurate modulation frequency. RF (Radio
Frequency) oscillator 32 may also be employed for this purpose. A
combination of oscillators is represented by dotted line block
104, entitled "OSCILLATOR".

[0029] An exemplary operating program for microprocessor 21 is
presented in flow chart form with reference to FIGS. 11 a-d of EP
0 592 851 B1 . In general, microprocessor 21 functions to control
controllable electromagnetic energy generator circuit 29 to
produce a desired form of modulated low energy electromagnetic
emission for application to a subject through applicator or probe
13.

[0030] Dotted line block 29, entitled CONTROLLABLE GENERATOR,
includes DDS modulation frequency generator 31 and carrier signal
oscillator 32. Microprocessor 21 operates to activate or
deactivate controllable generator circuit 29 through oscillator
disable line 33, as described in greater detail in EP 0 592 851 B1
. Controllable generator circuit 29 also includes an AM modulator
and power generator 34 which operates to amplitude modulate a
carrier signal produced by carrier oscillator 32 on carrier signal
line 36, with a modulation signal produced by modulation signal
generator circuit 31 on modulation signal line 37. The combination
of the functionality of the DDS modulation frequency generator 31,
with processor 21 with DAC, represented by dotted line block102,
enables output lines 33 and 37 to be combined to produce a single
signal. The combination furthermore enables arbitrary or periodic
wave forms of any shape to be generated, as similarly described in
EP 0 592 851 B1 .

[0033] As is illustrated and described in EU 0 592 851 B1
microprocessor 21 may select a desired waveform stored in a
modulation waveform storage device 43 and also controls a waveform
address generator 41 to produce on waveform address bus 42 a
sequence of addresses which are applied to modulation signal
storage device 43 in order to retrieve the selected modulation
signal. In the embodiment described in EP 0 592 851 B1 , the
desired modulation signal is retrieved from modulation signal
storage device 43 and applied to modulation signal bus 44 in
digital form. Modulation signal bus 44 is applied to wave form
generator and Digital to Analog Converter (DAC) 46 which converts
the digital modulation signal into analogue form. This analogue
modulation signal is then applied to a selective filter 47 which,
under control of microprocessor 21, filters the analogue
modulation signal by use of a variable filter network including
resistor 48 and capacitors 49 and 51 in order to smooth the wave
form produced by DAC 46 on modulation signal line 20.

[0034] A further embodiment possibility is a combination of
PROCESSOR WITH DAC dotted line block 102 with OSCILLATOR dotted
line block 104 or with a combination of oscillators 26 and 26A.
With such a combination, the hardware solution described in EP 0
592 851 B1 can be is realized internally in the processor 102 with
multiple outputs 33 and 37 or a single output combining these
signals.

[0035] The above embodiment from EP 0 592 851 B1 is in part
replaced by the functionality of the DDS modulation frequency
modulator 31. However, if it is determined that emissions of
different wave forms is desirable, it would be desirable to
include the modulation signal storage device 43 and wave form
generator 46 described in EP 0 592 851 B1 . Various modulation
signal wave forms may then be stored in modulation signal storage
device 43. Wave forms that have been successfully employed include
square wave forms or sinusoidal wave forms. Other possible
modulation signal wave forms include rectified sinusoidal,
triangular, or other wave forms and combinations of all of the
above.

[0036] The particular modulation control information employed by
microprocessor 21 to control the operation of controllable
generator circuit 29, is stored in application storage device 52.
The application storage device is conveniently a computer
comprising or being for receiving the information. Alternatively,
application storage devices illustrated and described in EP 0 592
851 B1 , with reference to FIGS. 12, 13, 14 and 15, may be
selected.

[0037] Interface 16 is configured as appropriate for the
particular application storage device 52 in use. Interface 16
translates the control information stored in application storage
device 52 into a usable form for storage within the memory of
microprocessor 21 to enable microprocessor 21 to control
controllable generator circuit 29 to produce the desired modulated
low energy emission.

[0038] Interface 16 may directly read the information stored on
application storage device 52, or it may read the information
through use of various known communications links. For example,
radio frequency, microwave, telephone, internet or optical based
communications links may be used to transfer information between
interface or receiver 16 and application storage device or
computer 52.

[0039] The system 11 may comprise a user identification device,
included in by block 21a in Figure 2. Conveniently, such a device
communicates with the one or more data processors or integrated
circuits 21 via interface 16, as shown. The user identification
device may be of any type, a finger print reader being an example.
Such a reader is for example available from Lenovo, 70563
Stuttgart, Germany, Part No. 73P4774.

[0040] The control information stored in application storage
device or computer 52 specifies various controllable parameters of
the modulated low energy RF electromagnetic emission which is
applied to a subject through applicator or probe 13. Such
controllable parameters include, for example, the frequency and
amplitude of the carrier, the amplitudes and frequencies and wave
forms of the modulation of the carrier, the duration of the
emission, the power level of the emission, the duty cycle of the
emission (i.e., the ratio of on time to off time of pulsed
emissions applied during a treatment), the sequence of application
of different modulation frequencies for a particular application,
and the total number of treatments and duration of each treatment
prescribed for a particular subject.

[0041] For example, the carrier signal and modulation signal may
be selected to drive the applicator or probe 13 with an amplitude
modulated signal in which the carrier signal includes spectral
frequency components below 1 GHz, and preferably between 1 MHz and
900 MHz, and in which the modulation signal comprises spectral
frequency components between 0.1 Hz and 10 KHz, and preferably
between 1 Hz and 1000 Hz. The one or more modulation frequencies
may be simultaneously emitted or sequenced to form the modulation
signal.

[0042] As an additional feature, an electromagnetic emission
sensor 53 may be provided to detect the presence of
electromagnetic emissions at the frequency of the carrier
oscillator 32. Emission sensor 53 provides microprocessor 21 with
an indication of whether or not electromagnetic emissions at the
desired frequency are present. Microprocessor 21 then takes
appropriate action, for example, by displaying an error message on
display 17, disabling controllable generator circuit 29, or the
like.

[0043] A power sensor 54 is preferably included which detects the
amount of power applied to the subject through applicator or probe
13 compared to the amount of power returned or reflected from the
subject. This ratio is indicative of the proper use of the system
during a therapeutic session. Power sensor 54 applies to
microprocessor 21 through power sense line 56 an indication of the
amount of power applied to patient through applicator or probe 13
relative to the amount of power reflected from the patient.

[0044] The indication provided on power sense line 56 may be
digitalized and used by microprocessor 21, for example, to detect
and control a level of applied power, and to record on application
storage device 52 information related to the actual treatments
applied to and received by the patient. Such information may then
be used by a physician or other clinician to assess patient
treatment compliance and effect. Such treatment information may
include, for example: the number of treatments applied for a given
time period; the actual time and date of each treatment; the
number of attempted treatments; the treatment compliance (i.e.,
whether the applicator or probe was in place or not during the
treatment session); and the cumulative dose of a particular
modulation frequency.

[0045] The level of power applied is preferably controlled to
cause the specific absorption rate (SAR) of energy absorbed by the
patient to be from 1 microWatt per kilogram of tissue to 50 Watts
per kilogram of tissue. Preferably, the power level is controlled
to cause an SAR of from 100 microwatts per kilogram of tissue to
10 Watts per kilogram of tissue. Most preferably, the power level
is controlled to cause an SAR of from 1 milliWatt per kilogram of
tissue to 100 milliWatts per kilogram of tissue. These SARs may be
in any tissue of the patient, but are preferably in the tissue of
the central nervous system.

[0046] System 11 also includes powering circuitry including
battery and charger circuit 57 and battery voltage change detector
58.

[0047] The RF carrier oscillator 32 produces a Radio Frequency
(RF) carrier frequency of 27 MHz. Other embodiments of the
invention contemplate RF carrier frequencies of 48 MHz, 433 MHz or
900 MHz. In general, the RF carrier frequency produced by carrier
oscillator 32 has spectral frequency components less than 1 GHz
and preferably between 1 MHz and 916 MHz (which is the upper limit
of the European 900 MHz band). Although the disclosed embodiment
contemplates that once set, the carrier oscillator frequency
remains substantially constant, the carrier frequency produced by
carrier oscillator 32 may be variable and controllable by
microprocessor 21 by use of stored or transmitted control
information.

[0048] Carrier oscillator 32 produces on carrier signal line 36 a
carrier signal which is then modulated by the modulation signal
carried on signal line 37.

[0049] Oscillator disable line 33 enables microprocessor 21 to
disable the signal from oscillator 32 by applying an appropriate
disable signal to oscillator disable line 33.

[0050] The output of the AM modulator and power generator 34
appears on signal line 38. This modulated signal is applied
through emitter output filter 39 which substantially reduces or
eliminates the carrier harmonics resulting from side effects of
the modulator and power generator circuit 34.

[0051] The output of the AM modulator and power generator 34 and
emitter output filter 39 may be designed to possess a 50 Ohm
output impedance to match a 50 Ohm impedance of coaxial cable 12.

[0052] It has been determined through impedance measurements that
when a probe 13 is applied within the mouth of a subject, the
probe/subject combination exhibits a complex impedance of the
order of 150+j200 Ohms. Impedance transformer 14 serves to match
this complex impedance with the 50 Ohm impedance of coaxial cable
12 and therefore the output impedance of the AM modulator 34 and
output filter 39. This promotes power transmission, and minimizes
reflections.

[0053] The arrangement described above has been optimized for a
contact probe with coupling to the mucosa of the mouth. In a
further example, a conductive, isolated probe has been used at a
frequency around 433 MHz coupling to the outer ear channel. Due to
the different probe design in such a frequency band and with this
coupling method, the values of matching elements (79 and 81
described in EP 0592 851 B1 ) would be different or could even be
omitted. Applicator or probe 13 may then be regarded as a
capacitive coupler or as an antenna matched to the capacitive
load.

[0054] As described in EP 0 592 851 B1 , with reference to the
flow charts of FIGS. 11 a-d, microprocessor 21 may operate to
analyse the signal appearing on power sense line 56 to determine
and control the amount of power applied to the patient, and to
assess patient treatment compliance, and possibly to record
indicia of the patient treatment compliance on application storage
device 52 for later analysis and assessment by a physician or
other clinician.

[0055] Exemplary of treatments performed on patients have included
breast, ovary, pancreas and liver tumour types. The treatments
involved applying a 27.12 MHz RF signal, amplitude modulated at
specifically defined frequencies ranging from 0.2 to 23,000 Hz at
very high precision and stability.

[0056] The following are synopses of abstracts for future
publications related to uses of electronic devices of the present
invention:

A phase I study of therapeutic amplitude-modulated electromagnetic
fields (THERABIONIC) in advanced tumors

[0058] Background: In vitrostudies suggest that low levels of
amplitude-modulated electromagnetic fields may modify cell growth.
We have identified specific frequencies that may block cancer cell
growth. We have developed the THERABIONIC device, a portable and
programmable device delivering low levels of amplitude-modulated
electromagnetic fields. The device emits a 27.12 MHz
radiofrequency signal, amplitude-modulated at cancer-specific
frequencies ranging from 0.2 to 23,000 Hz with high precision. The
device is connected to a spoon-like coupler, which is placed in
the patient's mouth during treatment.

[0059] Methods: We conducted a phase I study consisting of three
daily 40 min treatments. From March 2004 to September 2006, 24
patients with advanced solid tumors were enrolled. The median age
was 57.0 12.2 years. 16 patients were female. As of January 2007,
5 patients are still on therapy, 13 patients died of tumor
progression, 2 patients are lost to follow-up and one patient
withdrew consent. The most common tumor types were breast (7),
ovary (5) and pancreas (3). 22 patients had received prior
systemic therapy and 16 had documented tumor progression prior to
study entry.

[0060] Results: The median duration of therapy was 15.7 19.9 weeks
(range: 0.4-72.0 weeks). There were no NCI grade 2, 3 or 4
toxicities. Three patients experienced grade 1 fatigue during and
immediately after treatment. 12 patients reported severe pain
prior to study entry. Two of them reported significant pain relief
with THERABIONIC treatment. Objective response could be assessed
in 13 patients, 6 of whom also had elevated tumor markers. 6
additional patients could only be assessed by tumor markers. Among
patients with progressive disease at study entry, one had a
partial response for > 14.4 weeks associated with > 50%
decrease in CEA, CA 125 and CA 15-3 (previously untreated
metastatic breast cancer); one patient had stable disease for 34.6
weeks (add info); one patient had a 50% decrease in CA 19-9 for
12.4 weeks (recurrent pancreatic cancer). Among patients with
stable disease at enrollment, four patients maintained stable
disease for 17.0, > 19.4, 30.4 and > 63.4 weeks.

[0061] Conclusions: THERABIONIC is a safe and promising novel
treatment modality for advanced cancer. A phase II study and
molecular studies are ongoing to confirm those results.

[0063] Background : Phase I data suggest that low levels of
electromagnetic fields amplitude-modulated at specific frequencies
administered intrabucally with the THERABIONIC device are a safe
and potentially effective treatment for advanced cancer. The
device emits a 27.12 MHz RF signal, amplitude-modulated with
cancer-specific frequencies ranging from 0.2 to 23,000 Hz with
high precision. The device is connected to a spoon-like coupler
placed in the patient's mouth during treatment. Patients with
advanced HCC and limited therapeutic options were offered
treatment with a combination of HCC-specific frequencies.

[0064] Methods: From October 2005 to October 2006, 38 patients
with advanced HCC were recruited in a phase II study. The patients
received three daily 40 min treatments until disease progression
or death. The median age was 64.0 14.2 years. 32 patients were
male and 29 patients had documented progression of disease (POD)
prior to study entry.

[0065] Results: As of January 2007, 12 patients are still on
therapy, 20 patients died of tumor progression, 2 patients are
lost to follow-up and 3 patients withdrew consent. 27 patients are
eligible for response. The overall objective response rate as
defined by partial response (PR) or stable disease (SD) in
patients with documented POD at study entry was 31.6%: 3 PR and 9
SD. The median survival was 20.7 weeks with a median duration of
therapy of 17.5 weeks. 13 patients have received therapy for more
than six months. The median duration of response is 12.9 weeks. 12
patients reported pain at study entry: 8 of them (66%) experienced
decreased pain during treatment. There were no NCI grade 2/3/4
toxicities. One patient developed grade 1 mucositis and grade 1
fatigue.

Conclusion: In patients with advanced HCC THERABIONIC treatment is
a safe and effective novel therapeutic option, which has antitumor
effect and provides pain relief in the majority of patients.

[0066] The electronic device of the present invention, comprising
means for the accurate control over the frequencies and stability
of amplitude modulations of a high frequency carrier signal,
provides a safe and promising novel treatment modality for the
treatment of patients suffering from various types of advanced
forms of cancer.

EXAMPLES

Method and system for applying low energy emission
therapy US5441528

BACKGROUND OF THE INVENTION

The invention relates to systems and methods for applying low
energy emission therapy for the treatment of central nervous
system disorders.

Low energy emission therapy involving application of low energy
electromagnetic emissions to a patient has been found to be an
effective mode of treating a patient suffering from central
nervous system (CNS) disorders such as generalized anxiety
disorders, panic disorders, sleep disorders including insomnia,
circadian rhythm disorders such as delayed sleep, psychiatric
disorders such as depression, obsessive compulsive disorders,
disorders resulting from substance abuse, sociopathy, post
traumatic stress disorders or other disorders of the central
nervous system. Apparatus and methods for carrying out such
treatment are described in U.S. Pat. Nos. 4,649,935 and 4,765,322,
assigned to the same assignee as the present application, the
disclosures of which are expressly incorporated herein by
reference. Since the time of these earlier disclosures, a
substantially greater understanding of the mechanisms of the
treatment and how to secure best results has been gained, which
has led to important developments being made to the apparatus
(herein described as a system).

Although the apparatus and methods described in the above patents
have provided satisfactory results in many cases, consistency and
significance of results has sometimes been lacking. Also, it was
not always possible to properly control or monitor the duration of
treatment or the quantities or nature of the low energy emissions
being applied to the patient. Furthermore, the efficiency of
transfer of the low energy emissions to the patient was limited
and was affected by such factors as patient movement, outside
interference and the like.

Another limitation of the previously described apparatus is that
it is not very amenable to ready marketing by marketing
organizations specifically of the nature comprised in the
pharmaceutical industry. The apparatus is intended for therapy or
treatment of patients and the low energy emissions applied to the
patient are akin to pharmaceutical medication. The marketing
organization of a pharmaceutical industry should thus be placed in
a position to market the therapy in a fashion not widely different
from the fashion in which pharmaceutical products are marketed,
e.g., through pharmacists, with or without a doctor's
prescription.

Research on treatment for insomnia has lagged behind other medical
research programs. Current treatment methods for insomnia consist
either of hypnotics, behavioral therapies (e.g. biofeedback), or
of the use of drug agents, specifically benzodiazepines or
imidazopyridines. Tolerance, dependence, memory loss, and lack of
efficacy in long-term treatment are among the most common
drawbacks of these classes of currently available hypnotics.

Research throughout the past two decades has shown clearly that
the brain serves not only as a communication link and
thought-processing organ, but also as the source of significant
chemical activity, as well as a number of bioactive compounds.
Many of these neurotransmitter compounds and ions are secreted
following chemical or electrical stimuli. Research has also shown
that some of these neuroactive compounds are involved in the
regulation of sleep and wake cycles (Koella, "The Organization and
Regulation of Sleep," Experientia, 1984; 40(4): 309-408).

During the 1970s, Adey and his group demonstrated that weak
electromagnetic fields, modulated at certain well-defined low
frequencies, were able to modify the release of ions (calcium) and
neurotransmitters (GABA) in the brain (Kaczmarek and Adey, "The
Eflux of @45 Ca@2+ and [@3 H]y-aminobutyric Acid from Cat Cerebral
Cortex," Brain Research, 1973; 63:331-342; Kaczmarek and Adey,
"Weak Electronic Gradients Change Ionic and Transmitter Fluxes in
Cortex," Brain Research, 1974; 66:537-540; Bawin et al., "Ionic
Factors in Release of @45 Ca@2+ From Chicken Cerebral Tissue by
Electromagnetic Fields," Proceedings of the National Academy of
Science, 1978; 75(12):6314-6318). In these experiments the cortex
of anaesthetized cats was initially incubated with radio-labeled
calcium and radio-labeled GABA. When the cortex was exposed to
continuous stimulation by weak electric fields modulated at 200
Hz, the researchers found a 1.29-fold increase in Ca++ and a
1.21-fold increase in GABA release (Kaczmarek and Adey, Brain
Research, 1973; 63:331-342). Interestingly, the release of GABA
happened in parallel with the release of Ca++, suggesting that the
two phenomena are closely linked. The findings of increased Ca++
release from brain tissue upon stimulation with modulated
electromagnetic fields have been replicated (Dutta et al.,
"Microwave Radiation Induced Calcium Ions Effused from Human
Neuroblastoma Cells in Culture," Bioelectromagnetics, 1984;
5(1):71-78; and Blackman et al., "Influence of Electromagnetic
Fields on the Efflux of Calcium Ions from Brain Tissue in Vitro,"
Bioelectromagnetics, 1988; 9:215-227). It now has become an
established fact that weak electric fields modulated at certain
low frequencies are able to modulate the release of Ca++ and GABA.

During 1983, it was discovered that weak electromagnetic fields,
modulated at low frequencies and delivered by means of an antenna
placed in the buccal cavity, caused changes in EEG readings in
human volunteers. In agreement with the findings of Adey and
Blackman, it was found that only certain well-defined low
frequency modulations of a standard carrier frequency (27 MHz),
emitted with a well-defined intensity, were capable of eliciting
EEG changes.

SUMMARY OF THE INVENTION

The present invention has rendered feasible an entirely new
approach to treatment of a patient described in our said earlier
patents while avoiding the above-noted drawbacks.

The present invention contemplates provision in the system
(apparatus) of an interface for an application storage device,
which application storage device can comprise storage media, such
as, magnetic storage media, semiconductor memory storage media,
optical memory storage media, or mechanical storage media. The
selected storage media is programmed to carry various control
information. Other information which may be stored in the storage
media includes duration control information which would control
the duration of the low energy electromagnetic emission and hence
the duration of the application of the emission to the patient.
Further control information can include duty cycle control
information which would control the emissions, for example, in
such a fashion that the low energy emission is alternately
discontinued and re-initiated for chosen periods of time. Yet
further control information which may be programmed into the
storage media includes selecting information which would select
emissions of various different modulation waveforms and
frequencies which emissions can be emitted sequentially, with or
without pauses between the emissions. Still further control
information that may be programmed into the storage media includes
power level control information.

In one embodiment of the invention, the system includes a
microprocessor into which is loaded control information from the
application storage device. The microprocessor then controls the
function of the system to produce the desired therapeutic
emission.

Another embodiment of the present invention contemplates that the
application storage device would be combined into a single unit,
and would be connected to the system through an interface in order
to control the system.

In either of these embodiments, the present invention contemplates
that the interface may include a communications channel such as,
for example, a radio frequency link or telephone line, which
connects the application storage device to the rest of the system.

The present invention also contemplates provision in the system of
an impedance transformer connected intermediate the emitter of low
energy electromagnetic emissions and a probe for applying the
emissions to the patient, which impedance transformer
substantially matches the impedance of the patient seen from the
emitter circuit with the impedance of the output of the emitter
circuit.

Another aspect of the present invention is the provision of a
power reflectance detector which detects an amount of power
applied to a patient and compares that amount to an amount of
power emitted by the system. The power detector permits the
monitoring of patient compliance with the prescribed treatment.
Such patient treatment compliance information may be stored on the
application storage device for later retrieval and analysis. For
example, the power detector may be used to detect the number of
treatments applied to a particular patient, and the elapsed time
for each treatment. Further, the actual time of day of each
treatment may also be recorded, as may the number of attempted
treatments.

These and other features and advantages of the present invention
will become apparent to those of skill in this art with reference
to the appended drawings-and following details description.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a system for applying
modulated low energy electromagnetic emission to a patient, in
accordance with the present invention.

FIG. 2 is a block diagram of the
circuitry of the system of FIG. 1.

FIG. 3 is a detailed schematic of
the modulation signal generator of the circuit of FIG. 2.

FIG. 4 is a detailed schematic of
the modulation signal buffer and the carrier oscillator circuit
used in the circuit of FIG. 2.

FIG. 5 is a detailed schematic of
the AM modulation and power generator and output filter of the
circuit of FIG. 2.

FIG. 6 is a detailed schematic of
the impedance transformer of the circuit of FIG. 2.

FIG. 7 is a detailed schematic of
the emission sensor circuit of the circuit of FIG. 2.

FIG. 8 is a detailed schematic of
the output power sensor circuit used in the circuit of FIG. 2.

FIG. 9 is a detailed schematic of
the display module used in the circuit of FIG. 2.

FIG. 10 is a detailed schematic
of the power supply circuit used in the circuit of FIG. 2.

FIGS. 11 a-e are flow charts of
the method of operation of the system of FIG. 1 and 2, in
accordance with the present invention.

FIGS. 12, 13, 14, 15, 16 and 17
are examples of an application storage device for use with the
present invention.

DETAILED DESCRIPTION

Referring to FIG. 1, presented is a modulated low energy
electromagnetic emission application system 11, in accordance with
the present invention. As presented in prior U.S. Pat. Nos. 4,649,935 and
4,765,322, such a system has proven useful in the
practice of Low Energy Emission Therapy (LEET, a trademark of the
assignee of the present application), which involves application
of emissions of low energy radio frequency (RF) electromagnetic
waves and which has proven an effective mode of treating a patient
suffering from central nervous system (CNS) disorders such as, for
example, generalized anxiety disorders, panic disorders, sleep
disorders including insomnia, psychiatric disorders such as
depression, obsessive compulsive disorders, disorders resulting
from substance abuse, sociopathy, post traumatic stress disorders
or other disorders of the central nervous system. The system
includes a probe or mouthpiece 13 which is inserted into the mouth
of a patient under treatment. Probe 13 is connected to an
electromagnetic energy emitter (see also FIG. 2), through coaxial
cable 12 and impedance matching transformer 14. Although probe 13
is illustrated as a mouthpiece, any probe that is adapted to be
applied to any mucosa may be used. For example, oral, nasal,
optical, urethral, anal, and/or vaginal probes may be used without
departing from the scope of the invention. Probes situated closer
to the brain, for example endonasal or oral probes, are presently
preferred.

Application system 11 also includes an interface 16 which is
adapted to receive an application storage device 52 such as, for
example, magnetic media, semiconductor media, optical media or
mechanically encoded media, which is programmed with control
information used to control the operation of system 11 to apply
the desired type of low energy emission therapy to the patient
under treatment.

As presented in more detail below, application storage device 52
can be provided with a microprocessor which, when applied to
interface 16, operates to control the function of system 11 to
apply the desired low energy emission therapy. Alternatively,
application storage device 52 can be provided with a
microprocessor which is used in combination with microprocessor 21
within system 11. In such case, the microprocessor within device
52 could assist in the interfacing of storage device 52 with
system 11, or could provide security checking functions.

System 11 also includes a display 17 which can display various
indications of the operation of system 11. In addition, system 11
includes on and off power buttons 18 and 19.

It will be understood that configurations of application system 11
other than that presented in FIG. 1, may be used without departing
from the spirit and scope of the present invention.

Referring now to FIG. 2, presented is a block diagram of the
electronic circuitry of application system 11, in accordance with
the present invention. A data processor, such as for example,
microprocessor 21, operates as the controller for application
system 11, and is connected to control the various components of
the system 11 through address bus 22, data bus 23 and I/O lines
25.

Microprocessor 21 preferably includes internal storage for the
operation coded control program, and temporary data. In addition,
microprocessor 21 includes input/output ports and internal timers.
Microprocessor 21 may be, for example, an 8-bit single-chip
microcontroller, 8048 or 8051 available from Intel Corporation.

The timing for microprocessor 21 is provided by system clock 24
which includes a clock crystal 26 along with capacitors 27 and 28.
System clock 24 may run at any clock frequency suitable for the
particular type of microprocessor used. In accordance with one
embodiment of the present invention, system clock 24 operates at a
clock frequency of 8.0 MHz.

The operating program for microprocessor 21 is presented below in
flow chart form with reference to FIGS. 11 a-d. In general,
microprocessor 21 functions to control controllable
electromagnetic energy generator circuit 29 to produce a desired
form of modulated low energy electromagnetic emission for
application to a patient through probe 13.

Controllable generator circuit 29 includes modulation frequency
generator circuit 31 and carrier signal oscillator 32.
Microprocessor 21 operates to activate or de-activate controllable
generator circuit 29 through oscillator disable line 33, as
described below in more detail. Controllable generator circuit 29
also includes an AM modulator and power generator 34 which
operates to amplitude modulate a carrier signal produced by
carrier oscillator 32 on carrier signal line 36, with a modulation
signal produced by modulation signal generator circuit 31 on
modulation signal line 37.

Modulator 34 produces an amplitude moduated carrier signal on
modulated carrier signal line 38, which is then applied to the
filter circuit 39. The filter circuit 39 is connected to probe 13
via coaxial cable 12 and impedance transformer 14.

Microprocessor 21 controls modulation signal generator circuit 31
of controllable generator circuit 29 through address bus 22, data
bus 23 and I/O lines 25. In particular, microprocessor 21 selects
the desired waveform stored in modulation waveform storage device
43 via I/O lines 25. Microprocessor 21 also controls waveform
address generator 41 to produce on waveform address bus 42 a
sequence of addresses which are applied to modulation signal
storage device 43 in order to retrieve the selected modulation
signal. The desired modulation signal is retrieved from modulation
signal storage device 43 and applied to modulation signal bus 44
in digital form. Modulation signal bus 44 is applied to digital to
analog converter (DAC) 46 which converts the digital modulation
signal into analog form. This analog modulation signal is then
applied to selective filter 47 which, under control of
microprocessor 21, filters the analog modulation signal by use of
a variable filter network including resistor 48 and capacitors 49
and 51 in order to smooth the wave form produced by DAC 46 on
modulation signal line 20.

In the present embodiment, the various modulation signal wave
forms are stored in modulation signal storage device 43. With a 2
kilobyte memory, storage device 43 can contain up to 8 different
modulation signal wave forms. Wave forms that have been
successfully employed include square wave forms or sinusoidal wave
forms. Other possible modulation signal wave forms include
rectified sinusoidal, triangular, and combinations of all of the
above.

In the present embodiment, each modulation signal wave form uses
256 bytes of memory and is retrieved from modulation signal
storage device 43 by running through the 256 consecutive
addresses. The frequency of the modulation signal is controlled by
how fast the wave form is retrieved from modulation signal storage
device 43. In accordance with the present embodiment, this is
accomplished by downloading a control code from microprocessor 21
into programmable counters contained within wave form address
generator 41. The output of the programmable counters then drives
a ripple counter that generates the sequence of 8-bit addresses on
the wave form address bus 42.

Wave form address generator 41 may be, for example, a programmable
timer/counter uPD65042C, available from NEC. Modulation signal
storage device 43 may be, for example, a type 28C16 Electrical
Erasable Programmable Read Only Memory (EEPROM) programmed with
the desired wave form table. Digital to analog converter 46 may
be, for example, a DAC port, AD557JN available from Analog
Devices, and selective filter 47 may be a type 4052 multiplexer,
available from National Semiconductor or Harris Semiconductor.

The particular modulation control information used by
microprocessor 21 to control the operation of controllable
generator circuit 29, in accordance with the present invention, is
stored in application storage device 52. As presented below in
more detail with reference to FIGS. 12, 13, 14 and 15, application
storage device 52 may be any storage device capable of storing
information for later retrieval. For example, application storage
device 52 may be, for example, a magnetic media based storage
device such as a card, tape, disk, or drum. Alternatively,
application storage device 52 may be a semiconductor memory-based
storage device such as an erasable programmable read only memory
(EPROM), an electrical erasable programmable read only memory
(EEPROM) or a non-volatile random access memory (RAM). Another
alternative for application storage device 52 is a mechanical
information storage device such as a punched card, cam, or the
like. Yet another alternative for application storage device 52 is
an optical storage device such as a compact disk read only memory
(CD ROM).

It should be emphasized that although the figures illustrate
microprocessor 21 separate from .application storage device 52,
microprocessor 21 and application storage device 52 may both be
incorporated into a single device, which is loaded into system 11
to control the operation of system 11 as described herein. In this
case, interface 16 would exist between the combination of
microprocessor 21 and application storage device 52 and the rest
of system 11.

Interface 16 is configured as appropriate for the particular
application storage device 52 in use. Interface 16 translates the
control information stored in application storage device 52 into a
usable form for storage within the memory of microprocessor 21 to
enable microprocessor 21 to control controllable generator circuit
29 to produce the desired modulated low energy emission.

Interface 16 may directly read the information stored on
application storage device 52, or it may read the information
through use of various known communications links. For example,
radio frequency, microwave, telephone or optical based
communications links may be used to transfer information between
interface 16 and application storage device 52.

When application storage device 52 and microprocessor 21 are
incorporated in the same device, interface 16 is configured to
connect microprocessor 21 to the rest of system 11.

The control information stored in application storage device 52
specifies various controllable parameters of the modulated low
energy RF electromagnetic emission which is applied to a patient
through probe 13. Such controllable parameters include, for
example, the frequency and amplitude of the carrier, the
amplitudes and frequencies of the modulation of the carrier, the
duration of the emission, the power level of the emission, the
duty cycle of the emission (i.e., the ratio of on time to off time
of pulsed emissions applied during an application), the sequence
of application of different modulation frequencies for a
particular application, and the total number of treatments and
duration of each treatment prescribed for a particular patient.

For example, the carrier signal and modulation signal may be
selected to drive the probe 13 with an amplitude modulated signal
in which the carrier signal includes spectral frequency components
below 1 GHz, and preferably between 1 MHz and 900 Mhz, and in
which the modulation signal comprises spectral frequency
components between 0.1 Hz and 10 KHz, and preferably between 1 Hz
and 1000 Hz. In accordance with the present invention, one or more
modulation frequencies may be sequenced to form the modulation
signal.

As an additional feature, an electromagnetic emission sensor 53
may be provided to detect the presence of electromagnetic
emissions at the frequency of the carrier oscillator 32. Emission
sensor 53 provides to microprocessor 21 an indication of whether
or not electromagnetic emission at the desired frequency are
present. As described below in more detail, microprocessor 21 then
takes appropriate action, for example, displaying an error message
on display 17, disabling controllable generator circuit 29, or the
like.

The invention also includes a power sensor 54 which detects the
amount of power applied to the patient through probe 13 compared
to the amount of power returned or reflected from the patient.
This ratio is indicative of the proper use of the system during a
therapeutic session. Power sensor 54 applies to microprocessor 21
through power sense line 56 an indication of the amount of power
applied to patient through probe 13 relative to the amount of
power reflected from the patient.

The indication provided on power sense line 56 may be digitized
and used by microprocessor 21, for example, to detect and control
a level of applied power, and to record on application storage
device 52 information related to the actual treatments applied.
Such information may then be used by a physician or other
clinician to assess patient treatment compliance and effect. Such
treatment information may include, for example: the number of
treatments applied for a given time period; the actual time and
date of each treatment; the number of attempted treatments; the
treatment compliance (i.e., whether the probe was in place or not
in place during the treatment session); and the cumulative dose of
a particular modulation frequency.

The level of power applied is preferably controlled to cause the
specific absorption rate (SAR) of energy absorbed by the patient
to be from 1 microWatt per kilogram of tissue to 50 Watts per
kilogram of tissue. Preferably, the power level is controlled to
cause an SAR of from 100 microWatts per kilogram of tissue to 10
Watts per kilogram of tissue. Most preferably, the power level is
controlled to cause an SAR of from 1 milliWatt per kilogram of
tissue to 100 milliWatts per kilogram of tissue. These SARs may be
in any tissue of the patient, but are preferably in the tissue of
the central nervous system.

System 11 also includes powering circuitry including battery and
charger circuit 57 and battery voltage change detector 58.

FIGS. 3-10 present in more detail various components of the system
of FIG. 2.

Microprocessor 21 controls extended I/O lines 45 and selects the
desired wave form from wave form storage device 43. Microprocessor
21 then downloads the control information to the wave form address
generator 41 which in turn generates a sequence of the wave form
addresses. The sequence of addresses are then applied to the
modulation signal storage device 43 through address bus 42. The
desired modulation signal is then retrieved from the storage
device 43 and appears on signal bus 44 in digital form. After a
digital to analog conversion by the digital to analog converter
46, the modulation signal is filtered and is output onto the
modulation signal line 20.

The frequency of the modulation signal is determined by the rate
at which the sequence of wave form addresses is generated. The
type of modulation signal is selected by microprocessor 21 via
extended I/O lines 45 and the filtering network is selected via
I/O line 50.

Referring now to FIG. 4, presented is a detailed schematic of the
modulation signal buffer amplifier 35 and the carrier frequency
oscillator circuit 32.

The modulation signal buffer amplifier 35 is basically a
non-inverting amplifier in discrete form. The amplifier buffers
the modulation signal 20 from the selective filter 47 and provides
necessary modulation signal amplitude and current drive to the AM
modulator and power generator circuit 34. The output stage is
designed in such a way that the output signal 37 achieves a
rail-to-rail voltage swing. The output of the modulation signal
buffer appears on signal line 37.

It should be noted that although the disclosed embodiment
contemplates that the gain of modulation signal buffer amplifier
35 is substantially constant, the invention also contemplates use
of a variable gain amplifier that is controlled by microprocessor
21 in order to vary the magnitude of the modulation signal on line
37, thus permitting programmable control of the level of power
applied.

The carrier oscillator 32 is constructed around carrier oscillator
crystal 59. In one embodiment, carrier oscillator 32 produces a
Radio Frequency (RF) carrier frequency of 27 MHz. Other
embodiments of the invention contemplate RF carrier frequencies of
48 MHz, 450 MHz or 900 MHz. In general, the RF carrier frequency
produced by carrier oscillator 32 has spectral frequency
components less than 1 GHz and preferably between 1 MHz and 900
MHz. It should also be noted that while the disclosed embodiment
contemplates that once set, the carrier oscillator frequency
remains substantially constant, the present invention also
contemplates that carrier frequency produced by carrier oscillator
32 is variable and controllable by microprocessor 21 by use of
control information stored on application storage device 52. This
would be accomplished, for example, by use of high frequency
oscillator, the output of which is conditioned by a controllable
clock divider circuit to produce a controlled carrier frequency
signal.

Carrier oscillator 32 produces on carrier signal line 36 a carrier
signal which is to be modulated by the modulation signal carried
on signal line 37.

Oscillator disable line 33 is applied to NAND gate 61, the output
of which is applied to NAND gate 62. This configuration allows
microprocessor 21 to disable both modulation signal buffer 35 and
carrier oscillator 32 by applying an appropriate disable signal to
oscillator disable line 33.

FIG. 5 presents a detailed schematic of the AM modulator and power
generator 34 and the output filter 39. The AM modulator is made up
of two transistors 66 and 67 connected in parallel and operated in
zero-crossing switching mode. The carrier signal 36 is applied at
the bases of the transistors 66 and 67 through NAND gates 63 and
64, and the modulation signal 37 is applied to the collectors of
transistors 66 and 67 through inductors 68 and 69. The net result
is the modulated carrier that appears at the collectors of the
transistors 66 and 67.

The output power is generated by a single-ended tuned resonant
converters configured by three pairs of inductors and capacitors,
70, 71 and 72. LC resonant circuits 70, 71 and 72 are tuned to
provide the required output power and are optimized to the maximum
efficiency of the converter.

The output of the AM modulator and power generator 34 appears on
signal line 38. This modulated signal is applied through output
filter network 39 to output connector 78. Output filter 39
included three LC filtering stages, 73, 74 and 76.

The first LC filtering stage, 73 is a band-pass and band-notch
filter with pass band centered at 27 MHz and band notch centered
at 54 MHz. The band-notch filter provides additional suppression
to the second harmonic of the carrier. The second and third LC
filtering stages 74 and 76 are both band pass filters which have
pass band centered at 27 MHz. The three stage output filter serves
to substantially eliminate the carrier harmonics that result from
zero-crossing switching of the AM modulator circuit 34.

The output series resistor 77 is used to adjust the output
impedance of the modulator. It is found from measurement that the
output impedance of the AM modulator is considerably lower than 50
ohm. The series resistor 77 adjusts the output impedance of the
circuit is approximately 50 ohms.

FIG. 6 presents the details of the impedance transformer 14.
Referring also to FIGS. 1, 2, and 5, the output of the AM
modulator and power generator 34 and filter stage 39 is designed
to have a 50 Ohm output impedance which is chosen to match the 50
Ohm impedance of coaxial cable 12. Impedance transformer 14
includes inductor 79 connected between probe 1 and the middle
conductor of coaxial cable 12, and a capacitor 81 connected
between probe 13 and the ground conductor of coaxial cable 12.

It has been determined through impedance measurements that when
probe 13 is applied to the mouth of a patient, the probe/patient
combination exhibits a complex impedance on the order of 150+j200
Ohms. Impedance transformer 14 serves to match this complex
impedance with the 50 Ohm impedance of coaxial cable 12 and
therefore the output impedance of the AM modulator 34 and output
filter 39. This promotes power transmission, and minimizes
reflections. In one embodiment, inductor 79 is 0.68 microHenry,
and capacitor 81 is 47 picoFarads.

FIG. 7 presents the detailed schematic of the emission sensor 53
of the present invention. Emission sensor 53 includes antenna 82
which is capable of detecting electromagnetic fields at the
frequency of the carrier oscillator 32. The signal induced by
antenna 82 is applied to a simple diode detector formed by diode
83, capacitor 84 and resistor 85. The demodulated low frequency
signal is then applied to the base of a transistor 86 operating as
a switch. The output is a low level signal line 87 which is
connected to microprocessor 21. Emission sensor 53 is used at the
beginning of a treatment session to detect whether probe 13 is
emitting electromagnetic fields of the carrier frequency. If so,
microprocessor 21 produces on display 17 an indication that the
proper electromagnetic field is being produced.

Emission sensor 53 is also connected to the power supply circuitry
through EXT DC IN line 115 (see also, FIG. 10). When external dc
power is applied, line 115, which is connected to the base of
transistor 86, turns transistor 86 on, thus providing an
indication to microprocessor 21 that external dc power is applied.

Referring now to FIG. 8, presented is a schematic of the power
sensor 54 used to sense the ratio of the power applied to the
patient through probe 13 to the power reflected from the patient.
This ratio is indicative of the efficiency of power transfer from
the application system 11 to the patient, and may be used to
assess patient treatment compliance. Power sensor 54 may also be
used to monitor the level of power being applied to the patient.

Power sensor 54 includes bi-directional coupler 88 which can be,
for example, a model KDP-243 bi-directional coupler available from
Synergy Microwave Corporation. Bi-directional coupler 88 operates
to couple a portion of the energy emitted by application system 11
through output connected 78 and carried by coaxial cable 12 into
detecting circuits 89 and 90.

Output connector 78 is connected to a primary input of
bi-directional coupler 88 and co-axial cable 12 is connected to a
primary output of bi-directional coupler 88. Bi-directional
coupler 88 includes two secondary outputs, each of which are
connected to respective detecting circuits 89 and 90. Detecting
circuit 89 functions to detect the amount of power applied to the
patient, and detecting circuit 90 functions to detect the amount
of power reflected from the patient. Detecting circuit 89 is
connected through resistive divider 94 to the positive input of
differential amplifier 91. Detecting circuit 90 is connected
through resistive divider 92 to the negative input of differential
amplifier 91. The output of differential amplifier 91 is
indicative of the difference between the power transmitted to the
patient by application system 11, and the power reflected from the
patient, and thus is indicative of an amount of power absorbed by
the patient. The output of differential amplifier 91 is applied to
an analog to digital converter (ADC) or comparator 93, the output
of which connected to microprocessor 21 through power sense line
56.

As described in more detail below with reference to the flow chart
of FIGS. 11 a-d, microprocessor 21 operates to analyze the signal
appearing on power sense line 56 to determine and control the
amount of power applied to the patient, and to assess patient
treatment compliance, and possibly to record indicia of the
patient treatment compliance on application storage device 52 for
later analysis and assessment by a physician or other clinician.

FIG. 9 presents a detailed schematic of the information output
circuit 17. Microprocessor 21 controls the display module 109 of
information output circuit 17 via data bus 23 and address bus 22
and controls the sound control circuit 110 by an I/O line 100. The
display module 109 may be an intelligent LED display module
PD3535, available from Siemens or a LCD graphics module available
from Epson. The sound control circuit 110 may be a buzzer as shown
in FIG. 9 or it may be an advanced speech synthesizer.

Referring now to FIG. 10, presented are the details of the power
supply circuit used in the application system 11 of the present
invention.

During operation of application system 11, power is derived from
rechargeable battery 95 which may be, for example, a six volt
rechargeable Ni--Cd battery, or the like. Battery 95 is connected
through relay 99 to relay 98. The coil of relay 98 is powered by
transistor 106 which is controlled by the output of NAND gate 102.

NAND gates 102, 103, 104 and 105 are configured to form a
resettable latch. When on button 18 is depressed, the latch turns
on transistor 106 which activates the coil of relay 98. When off
button 19 is depressed, the latch is reset thus turning transistor
106 off, and removing power from the coil of relay 98.
Microprocessor 21 may also reset the latch by pulling low
momentarily on the Auto-Off line 107. This helps to save
unnecessary power consumption when the system 11 is being left in
an idle state.

When the coil of relay 98 is powered, battery 95 is connected to
voltage regulator 97 which provides regulated voltage Vcc which is
used to power various components of application system 11.

Connector 96 is provided to accommodate an external ac/dc adapter
(not shown) which is used to charge battery 95. When an external
dc adapter is connected to connector 96, voltage regulator 101
produces a regulated voltage which powers the coil of relay 99.
This causes battery 95 to be disconnected from voltage regulator
97, and causes the output of voltage regulator 101 to be connected
to the input of voltage regulator 97, thus permitting application
system 11 to be powered by the external dc adapter. An indication
of the existence of external dc voltage is applied to emission
sensor 53 (FIG. 7) through EXT DC IN line 115.

If external dc power is connected (determined by emission sensor
53 when application system 11 is initially powered),
microprocessor 21 executes the battery charging control routine,
stops controllable generator 29 and disables the carrier
oscillator 32. It also sends a signal to the battery charging
control 57 and turns on the fast charging circuits. A message is
displayed on display 17 or on a separate light emitting diode
indicating that the battery is being charged.

During the battery charging routine, microprocessor 21 constantly
monitors the battery voltage from the -dV detector 58 via data bus
23. Once the required -dV is detected, Ni--Cd battery 95 has
reached its full charge condition, microprocessor 21 switches off
the fast charge circuit and automatically removes power from the
system 11. -dV detector 58 may be configured, for example,
including a MAX166 digital to analog converter available from
Maxim Integrated Products, Inc.

The battery voltage is constantly monitored by the battery voltage
monitor 108. Once the battery voltage drops to a predetermined low
level (the voltage level at which the output emission power drops
by 3% of the calibrated value), a signal is provided to
microprocessor 21 which in turn stops the emission and provides an
error message on the display 17. Battery voltage monitor 108 may
be, for example, a voltage supervisory integrated circuit
available from Texas Instruments or SGS Thompson.

Referring now to FIGS. 11 a-d, presented are flow charts of the
operation of the application system 11 of FIGS. 1 and 2, in
accordance with the method of the present invention. In practice,
the flowcharts of FIGS. 11 a-d are encoded in an appropriate
computer program and loaded into the operating program storage
portion of microprocessor 21 in order to cause microprocessor 21
to control the function of application system 11.

Referring to FIG. 11a, microprocessor 21 starts execution of the
program when switch 18 is activated. In block 111, microprocessor
21 initializes the circuits by stopping the wave form address
generator 41, disabling the carrier oscillator 32 and displaying a
welcome message to the user on display module 109.

In block 112, the source of dc power is immediately checked
afterinitialization. If an external dc power source is connected,
for example an ac/dc adapter, it is assumed that system 11 should
function as a Ni--Cd battery charger. Microprocessor 21 passes
control to block 113 which switches on the fast charge mode of the
battery charging control 57 and monitors the battery voltage via
the -dV detector 58 in the control loop including blocks 111 and
116. Once the Ni-Cd battery 95 reaches its full-charged state as
detected by -dV detector 58, microprocessor 21 switches off the
fast charging current in block 117 and automatically switches off
system 11 in block 118.

If decision block 112 determines that external dc source is not
connected, system 11 is powered by the internal battery 95. The
battery voltage monitor 108 monitors the battery voltage at all
times and provides information to microprocessor 21 for use in
decision block 119. If the battery level drops to a predetermined
low level, microprocessor 21 displays an error message on the
display 109 in block 121. This is to inform the user to re-charge
the battery before using the system again. It also switches off
system 11 automatically in block 122 if there is no user response
as determined by timing loop 123.

Referring now to FIG. 11b, after the battery level is checked,
microprocessor 21 checks in block 124 if application storage
device 52 is connected to system 11 via interface 16. If
application storage device 52 is not connected, microprocessor 21
prompts for the application storage device 52 via information on
display 109 in block 126. The application storage device 52 must
be connected within a predetermined time limit as determined by
block 127, or microprocessor 21 switches system 11 off in block
128.

Once block 124 determines that application storage device 52 is in
place, microprocessor 21 reads an identification code in block 129
and checks if application storage device 52 is genuine and valid
in block 131. If not, an error message is displayed in block 132
and system 11 is switched off after a predetermined time limit.

If a valid application storage device is connected, microprocessor
21 reads the control information in block 133 and stores the
control information in the internal RAM area. Application
information such as the type of treatment may be displayed on
display 17 in block 134 for user re-confirmation. Microprocessor
21 then pauses and waits in block 136 for input from the user to
start the application.

The user starts the application by pressing the on switch 18
again. Microprocessor 21 generates a test emission in block 137 by
controlling the controllable generator 29 and prompts the user to
check the emission with emission sensor 53 in block 138.
Microprocessor 21 then checks the emission sensor input for the
indicative signal in block 139. If the emission is not detected
within a predetermined time limit as determined by block 142,
microprocessor 21 displays a corresponding error message in block
143 and switches off system 11 in block 144 after a predetermined
idle time as determined by block 146.

If the emission is detected within the predetermined time limit
determined by block 142, control a passes to block 147 where
microprocessor 21 executes the application software routine shown
in detail in the flowchart of FIGS. 11d and 11e.

The application software routine takes in the control information,
interprets the information and controls the controllable generator
29 to generate the corresponding modulation wave form, frequency,
power level, duration and duty cycle.

Referring to FIGS. 11d and 11e, microprocessor 21 starts the
routine by first setting up a total treatment time counter in
block 151 which keeps tracks of the timing of the actual
application. It then gets and interprets the first block of
modulating frequency data in block 152. Then, in block 153 the
modulation wave form is selected via extended I/O lines 45 and a
suitable filter network is selected via the extended I/O lines 50.
Also in block 153, the gain of modulation signal buffer amplifier
35 is adjusted in accordance with the power level control
information. In block 154, the modulation frequency is controlled
via the wave form address generator 41. The emission is then
enabled by microprocessor 21 in block 156.

In decision block 157, the battery is checked using battery
voltage monitor 108 to determine whether the battery level is
acceptable. If not, control passes to block 158 where an
appropriate error message is displayed. Then, system 11 is shut
down in block 161 after a delay time determined by decision block
159.

If, on the other hand, the battery voltage is acceptable, control
passes to decision block 162 where it is determined whether or not
application storage device 52 is still inserted in interface 16.
If not, control passes to decision block 163 where it is
determined whether a predetermined time has expired without the
presence of application storage device 52. When the time limit
expires, control passes to block 164 where an appropriate error
message is displayed, and eventually system 11 is automatically
shut down in block 161.

If, on the other hand, decision block 162 determines that
application storage device 52 is present within interface 16,
control passes to block 166 where application storage device 52 is
updated with user compliance information. Control then passes to
block 167 where the output of power sensor 54 is read. Control
then passes to block 168 where the output of power sensor 54 is
assessed to determine a level of power being applied to the
patient, and to assess whether or not treatment is being
effectively applied. For example, if sensor 54 determines the
presence of a large amount of reflected power, this condition may
possibly be indicative of probe 13 not being properly connected or
not being properly inserted into the mouth of a patient.

If decision block 168 determines that treatment is not being
properly applied, control passes to decision block 169 which
determines whether a predetermined time limit has been exceeded
without detection of proper treatment. If the time limit is
exceeded, control passes to block 171 where application storage
device 52 is updated with information indicative of non-compliance
with the treatment protocol.

If, on the other hand, decision block 168 determines that the
treatment it is being properly applied, control passes to block
172 where it is determined whether the end of the particular
modulation frequency block being applied has been reached. If not,
control returns to decision block 157. If, on the other hand,
decision block 172 determines that the end of the modulation
frequency block presently being applied has been reached, control
passes to decision block 173 where it is determined whether the
end of the treatment time has been reached. If so, control returns
to block 148 (FIG. 11c). If, on the other hand, decision block 173
determines that the end of the treatment session has not been
reached, control passes to block 174 where the next frequency
block is read from application storage device 52, and control
returns to block 153 for the continuation of the treatment
session.

At the end of the application routine, control is returned and the
microprocessor 21 displays an ending message in block 148 and
switches system 11 off automatically in block 149.

FIGS. 12, 13, 14, 15, 16 and 17 present exemplary configurations
for application storage device 52. It should be understood that
other configurations for application storage device 52 are also
possible, without departing from the spirit and the scope of the
present invention.

Referring to FIG. 12, application storage device 52 may comprise a
magnetically encoded card 181 which includes a magnetically
recordable portion 182 which stores the above-described control
information and patient treatment compliance information.

Referring to FIG. 13, application storage device 52 may comprise a
semiconductor memory 183 which is connected through terminals 184
to interface 16. Semiconductor memory 183 is used to store the
above described application control information and patient
treatment compliance information.

Referring now to FIG. 14, application storage device 52 may be in
the form of a smart card 186 with the semiconductor hidden behind
the contacts 187. The semiconductor may comprise only the memory
with some security control logic, or may also include a
stand-alone microprocessor that assists in communicating with the
host microprocessor 21 via interface 16.

As shown in FIG. 15, application storage device 52 may take the
form of a key-shaped structure 188 including semiconductor memory
189 and microprocessor 191 which are operatively connected to
electrical terminals 192.

FIG. 16 illustrates application storage device 52 in the form of a
compact disk read only memory (CDROM) 193, on which control
information is optically encoded.

Finally, as shown in FIG. 17, application storage device 52 may
take the form of a punched card 194, in which control information
is tangibly embodied in a pattern of punched holes 196.

TREATMENT EXAMPLES

The system of the invention for applying a modulated low-energy
electromagnetic emission to a patient, is useful for the treatment
of a patient suffering from central nervous system (CNS)
disorders. In use of the system, the probe for applying the
modulated carrier signal to the patient is connected to the
patient, in particular by means of a mouth piece probe placed in
the patient's mouth and the modulated low-energy electromagnetic
emission is applied to the patient through the probe. At least two
low-energy electromagnetic emissions modulated at different
frequencies are applied to the patient to achieve beneficial
results. Beneficially, several discrete electromagnetic emissions
modulated at different frequencies are applied to the patient for
a specific treatment of a CNS disorder. The time of treatment,
which relates to the amount of the low-energy electromagnetic
emission applied to the patient, may vary between wide limits
depending on the nature of the disorder being treated and the
effect desired. However, in general, the time of treatment would
be at least one minute per day and could continue over several
hours per day, but would normally be at most one hour per day.
Most preferably, the treatment time is at least ten minutes per
day which may be divided up into two or more application times,
e.g., of from five to forty-five minutes per application time.

EXAMPLE I

TREATMENT OF INSOMNIA

One of the specific CNS disorders which has been very
satisfactorily treated with the aid of the system of the invention
is sleep disorder, in particular insomnia which is the most
important sleep disorder. Clinical insomnia is defined by the
Diagnostic and Statistical Manual of Mental Disorders (DSM-III-R),
from the American Psychiatric Association 1987 (DSM-III-R):

"Diagnostic criteria for Insomnia Disorders
A. The predominant complaint is of difficulty in initiating or
maintaining sleep, or of non restorative sleep (sleep that is
apparently adequate in amount, but leaves the person feeling
unrested).
B. The disturbance in A occurs at least three times a week for at
least one month and is sufficiently severe to result in either a
complaint of significant daytime fatigue or the observation by
others of some symptom that is attributable to the sleep
disturbance, e.g., irritability or impaired daytime functioning.
C. Occurrence not exclusively during the course of "Sleep-Wake
Schedule Disorder or a Parasomnia."

"Diagnostic criteria for 307.42 Primary Insomnia
Insomnia Disorder, as defined by criteria A, B and C above, that
apparently is not maintained by any other mental disorder or any
known organic factor, such as a physical disorder, a Psychoactive
Substance Use Disorder, or a medication."

The frequencies of modulation for the low-energy electromagnetic
emissions applied to the patient for treating insomnia have been
found to be effective when comprising two or more frequency
modulations selected from the following bandwidths: 1-5 Hz, 21-24
Hz, 40-50 Hz, 100-110 Hz, or 175-200 Hz.

A very specific example of a set of low-energy electromagnetic
emissions applied to a patient suffering from insomnia are
modulated at the following frequencies and applied sequentially to
the patient for the times indicated over a period of 20 minutes
per day, three times a week or every day is as follows:
Protocol P40: about 2.7 Hz for about 6 seconds, followed by about
a 1 second pause, about 21.9 Hz for about 4 seconds, followed by
about a 1 second pause, about 42.7 Hz for about 3 seconds,
followed by about a 1 second pause, about 48.9 Hz for about 3
seconds, followed by about a 1 second pause.

A study employing the above protocol P40 set of frequency
modulations and times of application was performed to test the
efficacy of low-energy emission therapy (LEET) in the treatment of
insomnia.

EXAMPLE IA

TREATMENT OF INSOMNIA

The primary endpoints of the study were defined as measures of
sleep (total sleep time (TST) and sleep latency (SL)) as measured
by polysomnography (PSG). Secondary endpoints (also quantified by
PSG) included measures of rapid eye movement (REM), non-REM,
number of awakenings after sleep onset, and wake after sleep onset
(WASO). Additional measures of individual responses to treatment
were derived from the patients' reports.

METHODS:

The study was a placebo-controlled, double-blind,
repeated-measures study performed on a total of thirty subjects.
Treatment was provided via a 12 V battery-powered device in
accordance with the present invention, emanating the P40 protocol.

Forty-six subjects underwent polysomnographic (PSG) evaluation in
order to yield the thirty subjects who participated in the study.
The subjects who met the PSG criteria were randomized to treatment
groups by means of a coin flip. All 30 subject completed the
study. Subjects were identified for potential enrollment via
television and radio advertisement.

Each study subject completed a number of rating scales prior to
entry into and throughout the study. These scales included the
Hamilton Anxiety Rating Scale (HARS), the Profile of Mood States
(POMS), the Hopkins Symptom Check List (HSCL), and a patient
reported sleep rating scale. The HARS, POMS, and HSCL were
obtained during the initial psychiatric screening prior to entry,
on a weekly basis thereafter, and at completion of the study.
Daily sleep logs were maintained by patients throughout the study.
Patients received treatment 3 times per week over the 4 weeks of
the study, and were randomly assigned to either active or inactive
treatment groups, under double-blind conditions. Treatment was
performed with patients in a supine position, resting comfortably
on a bed in a sleep-recording room with a low level of
illumination.

ENTRY CRITERIA:

To qualify for a baseline PSG study, subjects were screened for
chronic insomnia of a non-medical etiology. Patients with active
medical illness, psychiatric diagnoses (DSM-III-R), alcohol/drug
addiction, or active use of benzodiazepines and/or tranquilizers
were excluded.

Entry into the study required patients to be suffering from
chronic insomnia (more than six months) and to meet at least 2 of
the 3 established PSG sleep criteria: sleep latency of greater
than 30 minutes duration; total sleep time (TST) of less than 360
minutes per night; sleep efficiency (total sleep time/total
recorded time) of less than 85%. Subjects were asked to go to bed
in the laboratory at their regular bedtime and were allowed to
sleep "ad libitum". The study was ended by the technician only if
the time in bed was greater than 8.5 hours and the subject at that
time was lying in bed awake.

STATISTICAL METHODS:

For purposes of statistical analysis, a Student's t-test was
performed comparing the difference in the change scores (post-pre)
between the treatment groups. Where appropriate, analyses were
adjusted for baseline values using linear regression.

RESULTS:

Base Line Evaluation

Of the 30 consenting, eligible patients, 15 were randomly assigned
to each of the treatment groups. In the active treatment group,
there were 4 men and 11 women (mean age of 39 years). In the
inactive treatment group there were 6 men and 7 women (mean age of
41 years). The mean age of the subjects did not differ
significantly between groups.

At baseline, by definition, all patients met criteria for severe
insomnia. Although the study groups had comparable patient
reported TST durations at baseline, the placebo group had a
significantly longer TST at baseline when measured by PSG. Both
groups had prolonged sleep latency periods at baseline (>20
mins) as determined by both patient reported and PSG measures.
Pre-treatment sleep parameters are summarized in Table II.

Post-Treatment Evaluation:
Interval Changes

All 30 patients completed the trial. In the placebo group, the PSG
TST decreases slightly at the conclusion of the study, compared
with baseline values (from 337.0.+-.57.2 to 326.0.+-.130.5 TST
change of -11.0.+-.122.8, p=0.74). Similarly, the pre- and
post-patient reported measures of TST were nearly identical in the
placebo group (from 269.0.+-.73.6 to 274.3.+-.103.2, TST change of
5.+-.122, p=0.87). In contrast, the PSG measured TST increased in
the active group by nearly 90 minutes (from 265.9.+-.67.5 to
355.8.+-.103.5, TST increase of 89.9.+-.93.9, p=0.002). This
finding is consistent with the patient reported improvement
reported by the active treatment group (from 221.7.+-.112.3 to
304.0.+-.144.7, TST increase of 82.3.+-.169.0 minutes, p=0.08).

Also worth noting is that, while the proportion of REM sleep in
the placebo group increased only slightly from 17.3 to 18.7% of
total sleep time, in the active group, it increased from 16.3 to
20.9% of the total sleep time. The patient reported measure of
sleep latency improved by more than 50% in the active treatment
group during the study (from 145.8.+-.133.2 to 70.7.+-.67.9,
p=0.03) while sleep latency increased slightly in the placebo
group during the study period (from 71.3.+-.41.2 to 82.8.+-.84.8,
p-0.58).

SIDE EFFECTS:

Side effects are summarized in Table I. One patient in the active
treatment group reported increased dreaming. No other side effects
were reported.

Subjects enrolled in this study demonstrated severely disturbed
sleep criteria by both patient reported and PSG measures. The
active treatment group exhibited an improvement of 34% in PSG TST,
while the placebo group demonstrated a 3% decrease in PSG TST. The
significant difference in TST changes between groups from baseline
was not explained solely by the significantly different baseline
TST of the active and placebo groups. Adding the baseline TST in a
regression model using treatment as a predictor did not adequately
account for the difference in TST between the treatment groups.

Patient reported measurements confirmed the PSG findings, with a
37% improvement in the active group TST compared with a 2%
improvements in the control group. Other PSG and patient reported
measures of sleep indicated consistently greater improvement in
the active group compared with the placebo group. Those results
indicate that LEET therapy (using the P40 program) on an
every-other-day basis, successfully treats insomnia by both
lengthening the total duration of sleep and shortening sleep
latency. Furthermore, patients felt that their sleep patterns were
improved. Post-treatment sleep parameters are summarized in Table
III.

Another double blind, patient-reported study was also designed to
test the efficiency of low-energy emission therapy (LEET) in the
treatment of insomnia of non-medical etiology.

The primary PSG of the study was to detect differences between the
treatment groups in perceived sleep measures (total sleep time and
sleep latency), as reported by the subjects.

METHODS:

The study was preformed on a total of 30 subjects. Treatment was
provided using the device of the present invention with the P40
protocol powered by a 12-volt battery. All patients completed all
phases of the study. In the inactive treatment group there were 8
males and 7 females (mean age of 40 years). In the active
treatment group there were 6 males and 9 females (mean age of 39
years). There were no significant differences in age between the
active treatment and inactive treatment populations.

Each study subject completed a number of rating scales prior to
entry into and throughout the study. These scales included the
Hamilton Anxiety Rating Scale (HARS), the Profile of Mood States
(POMS), the Hopkins Symptom Check List (HSCL), and a patient
reported sleep rating scale. The HARS, POMAS, and HSCL were
obtained during the initial psychiatric screening prior to entry,
on a weekly basis thereafter, and at completion of the study.
Daily patient reported sleep rating scales were maintained by
patients throughout the study. Patients received treatment 3 times
per week over the 4 weeks of the study and were randomly assigned
to either active or inactive treatment groups, under double-blind
conditions. Treatment was performed with patients in a supine
position, resting comfortably on a bed in a sleep-recording room
with a low level of illumination. Subjects continued to record
sleep log data for two weeks after discontinuation of treatment.

ENTRY CRITERIA:

Patients between 20 and 50 years of age were recruited into the
study. Entry into the study required patients to meet at least 2
of the 3 established sleep criteria: patient reported sleep
latency of greater than 30 minutes; patient reported total sleep
time of less than 360 minutes; and patient reported sleep
efficiency of less than 85% (calculated as TST/total time in bed).
Patients with active medical illnesses, psychiatric illnesses
(according to DSM-III-R), drug or alcohol dependence were
excluded.

STATISTICAL METHODS:

For the purposes of statistical analysis, a Student's t-test was
performed comparing the difference of the change scores (post-pre)
between each of the treatment groups.

RESULTS:

Throughout the course of the study, subjects were asked to
estimate their total sleep time and sleep latency. A comparison
was made between the patient reported sleep latency and the
patient reported total sleep time at the time of the telephone
interview, and the patient reported sleep latency and patient
reported total sleep time obtained in the morning following the
last night of treatment. A highly significant difference was seen
for total sleep time (two-sided p=0.0021), with a more than
threefold increase in the active group compared with the placebo
group. The active treatment group also exhibited a >50%
decrease in sleep latency as compared with the baseline. Patient
reports of sleep are summarized in Table IV.

No statistically significant differences were seen between the two
groups for any other measured parameter. There was no first or
second night rebound insomnia as assessed by changes in either
total sleep time or sleep latency. Furthermore, there is no
evidence of rebound effect during the two weeks following
discontinuation of treatment. Rebound insomnia analyses are
summarized in Table V.

Treatment with LEET using a battery powered system is highly
effective in the treatment of insomnia, based on patient reported
measurement of total sleep time.

PATIENT REPORTS OF SLEEP: Combined meta-analysis for the above two
insomnia studies.

A meta-analysis of the patients' reports of sleep from the two
studies is provided in Table VII. These studies were identical in
terms of inclusion and exclusion criteria and study design
(4-week, double-blinded, placebo-controlled). This analysis,
performed on data from 60 patients (30 per group) demonstrates a
52 minute decrease in sleep latency, in the active group versus no
change in the inactive group (p=0,025). Total sleep time increased
by 128 minutes in the active group versus 28 minutes in the
placebo group (p=0.005).

As discussed above, several discreet electromagnetic emissions
modulated at different frequencies are applied to a patient for a
specific treatment of a CNS disorder. Based on the statistically
significant improvements in total sleep time and sleep latency
reported above, a low-energy emission therapy (LEET) program has
been developed for a further CNS disorder, more closely defined as
generalized anxiety disorders and panic attacks. For this
indication, it has been determined that frequency modulations of
the low-energy electromagnetic emissions should be within the
following bandwidths: 1-5 Hz, 14-17 Hz, 40-50 Hz, and 175-200 Hz.
More specifically, a variety of discreet modulations are selected
from the above bandwidths and are applied for different times, one
specific example comprising: about 1.4 Hz for about 40 seconds,
about 2.8 Hz for about 20 seconds, about 3.4 Hz for about 15
seconds, and a separate group comprising: about 3.4 Hz for about
15 seconds, about 14.6 Hz for about 4 seconds, about 42.7 Hz for
about 2 seconds, about 48.9 Hz for about 2 seconds, and about
189.7 Hz for about 1 second.

For example, the first group of frequencies mentioned may be
applied to the patient sequentially for a period of about 15
minutes during the morning of each day of treatment, and the
second group of frequencies may be applied to the patient
sequentially for a period of about 30 minutes in the evening of
each day of treatment.

Exclusion criteria:
1. Meets DSM-III-R criteria for Substance Abuse in past three
months.
2. Known contraindication to low intensity magnetic field
(including pregnant patients or those planning to become pregnant
in near future)
3. Meets DSM-III-R criteria for Current Mania, Hypomania, or
Mixed-Episode Depression, Dysthymia, or Cyclothymia.
4. History of Panic Disorder, Obsessive Compulsive Disorder,
Schizophrenia,or Schizoaffective Disorder
5. Acute suicidal ideation at screening interview
6. Use of anxiolytic medication within one week of screening visit
7. Dosage of other psychoactive agents not stable during preceding
12 weeks
8. Has started new psychotherapy in the preceding six months
9. Plans to begin new psychotherapy during the course of the study

Subjects were given oral and written instructions for home use of
the LEET device. Treatment consisted of daily exposures of 15
minutes each morning and 30 minutes each evening. The devices were
pre-programmed to provide selected AM frequency RFEM waves via an
antenna which the subject placed against the roof of their mouths.
Subject were instructed to use the devices while recumbent with
their eyes closed. All ratings were performed under open
conditions. After six weeks of treatment, the devices were
collected. Patients returned for follow-up visits in the second
and fourth weeks after discontinuing treatment.

RESULTS:

Results are reported for the four women and six men who entered
the protocol. As Table VIII illustrates, mean Ham-A improved from
23.4 to 8.1 after the first week of treatment. By the third week
of treatment, nine of the ten subjects showed improvement on the
Ham-A of at least 50% of their baseline scores. Improvement was
generally sustained through the sixth week. After discontinuation,
the benefit of treatment appeared sustained in some subjects
through the post-treatment follow-up. Although many subjects
experienced some increase in Ham-A after discontinuing treatment,
no subject reported rebound anxiety. Mean scores on Ham-D also
improved from 15.01 at baseline and remained less than 6 after the
first week of treatment.

The results are noteworthy for several reasons. First, LEET is an
entirely new treatment paradigm which offers an attractive side
effect profile and the potential to treat anxiety and related
disorders. Second, the results are encouraging both in the
magnitude of the effect and in the percentage of patients who
achieved a clinically significant improvement. Third, the
possibility that all instances of observed efficacy are due to
placebo response is diminished by the duration of the observed
improvement and that several of the patients had failed to improve
in prior controlled studies and in previous open treatment with
high potency benzodiazepines and/or antidepressants. Further
research under double-blind conditions is indicated to further
establish the efficacy of LEET and to clarify its role in clinical
practice.

Although the invention has been described with reference to
certain embodiments, it will be understood by those of skill in
this art that additions, deletions and changes can be made to
these embodiments, without departing from the spirit and scope of
the present invention.